title: Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: Comparison between T790M mutation-positive and mutation-negative populations.
abstract: BACKGROUND
  The secondary epidermal growth factor receptor (EGFR) mutation Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Recent reports have demonstrated that the emergence of T790M predicts a favorable prognosis and indolent progression. However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M mutation.
  
  
  METHODS
  The study investigated 78 EGFR-mutant patients who had undergone rebiopsy after TKI failure. The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used in EGFR mutational analyses. Various patient characteristics and postprogression survivals (PPSs) after initial TKI failure were retrospectively compared in patients with and without T790M.
  
  
  RESULTS
  The T790M mutation was identified in 4 (17%) of 24 central nervous system lesions, and in 22 (41%) of 54 other lesions (P = .0417). No other characteristics had a statistical association with T790M prevalence. Median PPS was 31.4 months in 26 patients with T790M, and 11.4 months in 52 patients without T790M (P = .0017). In the multivariate analysis, statistically significant factors for longer PPS included T790M-positive, good performance status, and no carcinomatous meningitis.
  
  
  CONCLUSIONS
  The emergence of T790M in central nervous system lesions was rare, compared with other lesions. Patients with T790M after TKI failure appear to have better prognoses than those without T790M. TKI rechallenge or continuous administration beyond progression may be effective after initial TKI failure.
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Jumpei
authors.initials: J
authors.lastname: Takeshita
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nanjo
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Imai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Monden
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kazuma
authors.initials: K
authors.lastname: Nagata
authors.forename: Kyoko
authors.initials: K
authors.lastname: Otsuka
authors.forename: Ryo
authors.initials: R
authors.lastname: Tachikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.forename: Kei
authors.initials: K
authors.lastname: Kunimasa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwasaku
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy / Q000379:methods; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases
keywords: T790M; acquired resistance; epidermal growth factor receptor-tyrosine kinase inhibitor; non-small cell lung cancer; rebiopsy